Project Summary Respiratory Syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infection (ALRI), including bronchiolitis and pneumonia, globally. RSV disease in infancy is associated with substantial morbidity and mortality, and infants who experience severe RSV are at increased risk of recurrent wheeze and asthma later in life. American Indians and Alaska Natives (AI/AN), who experience many health disparities, are at substantially increased risk of RSV compared to the general US population. Numerous products for the prevention of RSV in infants and children are currently in late stage development, including maternal vaccines and monoclonal antibodies. Such interventions are urgently needed in AI/AN communities. Current CDC surveillance systems do not measure RSV illness in AI/AN populations. Furthermore, the burden of RSV in pregnant women and the effect it may have on pregnancy and delivery outcomes are poorly understood. Quantifying the current burden and characterizing the epidemiology of RSV disease in AI/AN children and pregnant women is a critical step to inform optimal use of RSV-prevention products to reduce disease and promote health equity. The proposed research will build upon long-standing collaborations between tribal partners, the Johns Hopkins Center for American Indian Health (JHCAIH) and the Alaska Native Tribal Health Consortium (ANTHC) to create the RSV Surveillance in Native Americans (RSV-SuNA) system. RSV-SuNA will quantify and describe RSV disease in AI/AN children under five years and pregnant women in three communities in the southwestern US and two communities in Alaska over five RSV seasons. The platform will consist of active, population- based, in-patient and outpatient surveillance for ALRI across multiple settings and seasons in order to provide a robust understanding of RSV disease in Native populations. Nasal swabs will be collected from consenting participants and tested for the presence of RSV and other pathogens associated with ALRI using validated laboratory methods. This, and the use of standardized case definitions and data collection in instruments, will facilitate comparison across sites and with other active surveillance networks (e.g. CDC?s existing New Vaccine Surveillance Network). This study will determine the age-specific incidence of RSV-associated hospitalizations and outpatient visits in these AI/AN communities and characterize RSV- and non-RSV associated ALRI, including risk factors, clinical course, and sequalae. The collaborative, multi-site approach will fill key gaps in our understanding of the epidemiology of RSV and produce meaningful data to inform policy and monitor RSV disease in AI/AN populations. The RSV-SuNA system could be replicated in other AI/AN populations and could be used after the introduction of RSV prevention products to quantify their impact on the burden of both RSV and non-RSV ALRI.